Oulu University Research Articles

Suture button versus syndesmosis screw fixation in pronation-external rotation ankle fractures: A minimum 6-year follow-up of a randomised controlled trial

ObjectiveRandomised controlled trials (RCT) with short-term follow-ups have shown that, in treatment of syndesmosis injuries, a suture button device (SB) resulted in better radiographic and functional outcome compared to syndesmosis screw fixation (SS). However, only one RCT has reported long-term results; thus, the syndesmosis malreduction rates for both implants might increase during longer follow-up. The primary objective of this RCT was to evaluate the maintenance of syndesmosis reduction with the SS compared to the SB fixation in patients during a minimum follow-up of 6-years. The secondary objectives were to assess the post-traumatic osteoarthritis (OA) grade and the functional outcome. Patients and MethodsAt Oulu University Hospital, between January 2010 and December 2011, we enrolled 43 patients with Lauge-Hansen pronation-external rotation type 4/Weber C, ankle fractures with unstable syndesmosis. Patients were randomised to treatment with either a single 3.5-mm tricortical SS (22 patients) or an SB (21 patients). The mean follow-up was 7.1 years (range, 6.2—7.9). Syndesmosis reduction and OA grade was assessed with standing cone-beam computed tomography (CBCT) of both ankles. Malreduction was defined as >2 mm side-to-side difference in the mean width of the syndesmosis. OA was graded according to the Morrey & Wiedeman classification. The Olerud-Molander Ankle Outcome Score (OMAS) and a quality of life questionnaire (RAND 36-Item Health Survey) were used to evaluate functional outcome. ResultsTwo syndesmoses in the SS group and one in the SB group were malreduced (P = 0.58). Moderate OA after a mean of 7 years post-injury was common. In the SS and SB groups, 9 of 16 and 11 of 13 patients, respectively, had one or more grades serious OA in the injured ankle than in the uninjured ankle (P = 0.11). The mean OMAS was 88 in the SS group and 78 in the SB group (difference between means 7.1, 95% CI: −7.0–21.1, P = 0.32). The RAND-36 results did not differ between groups. ConclusionThe SS and SB maintained syndesmosis reduction equally well during follow-up. Our study findings also suggest that both methods result in moderate OA rates and the functional outcome is comparable between these two syndesmosis fixation methods.

Toll-like receptor 5 and 8 in hepatocellular carcinoma.

Toll-like receptors (TLRs) are components of innate immunity, but also have a role in carcinogenesis. The prognostic value of TLR5 and TLR8 tumor expression was examined in contrast with known risk markers Ki67 and p53. All HCC patients from Oulu University Hospital with available representative tumor sample were included in this study (n=182). TLR5, TLR8, Ki67, and p53 expression were investigated by immunohistochemistry. The relation between patient survival and TLR, Ki67, and p53 expression was calculated with Cox regression adjusted for confounding factors. TLR5 cytoplasm intensity was associated with 5-year overall (strong 0.0% vs weak 23.4%, p<0.001) and disease-specific (strong 0.0% vs weak 34.9%, p<0.001) survival. TLR5 nuclei percentage was associated with poor 5-year disease-specific survival (high 16.3% vs low 31.5%, p=0.022). In adjusted analysis, strong TLR5 cytoplasm intensity was an independent risk factor for poor 5-year overall (adjusted HR 1.88, 95% CI 1.26-2.81) and disease-specific (adjusted HR 2.00, 95% CI 1.27-3.15) survival. High Ki67 and p53 expression associated with 5-year overall- and disease-specific survival. TLR8 was not associated with patient survival. This study suggests that TLR5 expression is independently prognostic in HCC with similar point estimate as previously known p53.

Treatment trends and outcomes of hepatocellular carcinoma in a single center for 35 years.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The aim of this study was to examine the trends of HCC treatment and the outcomes in a single tertiary center for 35 years. Two hundred seventy-three consecutive HCC patients between 1983-2018 were identified from Oulu University Hospital records. Primary outcomes of the study were postoperative complications within 30 days after the operation, and short- (30- and 90-day) and long-term (1, 3 and 5-year) survival. Of the 273 patients, 49 underwent surgical resection, 25 local ablation, 48 angiological treatment and 151 had palliative treatment. The rate of surgery declined over time, while other invasive treatments increased. Major complications occurred in 14 (28.6%) patients after surgical resection, in 2 (8.0%) patients after local ablation and in 13 (27.1%) patients after angiological treatment (P=0.022). Recurrence and local recidives were observed especially in local ablation group and in angiological treatment group (P<0.001). Overall survival rates in surgical resection group were at 30 and 90 days, 1-, 3- and 5-years 95.9%, 95.9%, 85.1%, 59.0% and 51.2%. In local ablation group, respective overall survival rates were 100.0%, 100.0%, 86.1%, 43.1% and 18.8%, and in angiological group 95.8%, 93.6%, 56.1%, 26.3% and 6.6%. In cox regression model adjusted for confounding factors, mortality hazard was lowest after surgical resection. Prognosis was poor in palliative group. Based on this Northern Finland population, the surgical resection of HCC has acceptable complication rate compared to other treatments; and yields the best long-term survival. Overall prognosis of HCC remains poor.

(Invited) Use of Secondary Materials in NMC Co-Precipitation: Effect of Impurities on the Cell Performance

The growing demand for raw materials in lithium-ion batteries increasingly requires the increased use of secondary raw materials in the co-precipitation of NMC battery chemicals. Traditionally, pure raw materials as metal solutions are required for co-precipitation, which is a challenge for battery producers. Removal of impurities is also expensive and challenging step. Aim of this research is to study the impact of impurities present in metal sulfate solutions on the battery cell performance. These metal sulfate solutions were obtained from metal industry’s side-stream and from recycled spent batteries.Metal sulfate solutions with known amount of impurities were used in (Ni0.8Co0.1Mn0.1)OH2 (NMC811) precursor co-precipitation. Commercial pure manganese and nickel sulfates were used as reference samples. Key impurities in the solutions were zinc, iron, calcium, potassium, lithium, and magnesium. Composition of samples was determined using ICP-OES. We also demonstrate actions to control precipitation of impurities during the NCM precursor co-precipitation. Solubilities of impurities were calculated using MEDUSA and HYDRA.Dried hydroxide precursor (sieved <25µm) was mixed with LiOH in molar ratio of Li:(Ni0.8Co0.1Mn0.1:Al) 1.04:0.996. LiOH excess was used to compensate lithium loss during high temperature calcination and ensure homogenous lithiation. The mixture calcined with 2.5°C/min heating ramp and 6 hours holding time at 800 °C under O2 flow. Material was milled and sieved <40µm in the dry room conditions. Residual lithium washed from surface with certain amount of de-ionized water and dried in vacuum oven.Cathode slurry was mixed with Thinky ARE 250 mixer. Slurry composition was 4% of PVDF, 4% carbon and 92% active material and NMP as solvent. Cathode slurry was spread on aluminum foil with 100 µm applicator, then dried at 50 °C for few hours and finally at vacuum oven at 120 °C overnight. Cathode foil was calendered three times before coin cell assembly. The active material loading on the foil was about 12 mg/cm2. Theoretical capacity used to calculate the C-rate was 200 mAh/g. Electrochemical performance was carried out using one electrode pair pouch cell (50 mAh) was prepared with graphite anode, and electrolyte was 1.15M LIPF6 in EC:DMC:EMC (2:4:4) and 1 % of vinylane carbonate. All foils and coin cells were prepared in the dry room. Cells tested between 4.2V-2.8V. 1100 cycles at 1C/1C currents including capacity check every 100 cycles at 0.2C/0.2C currents. Before the capacity check, cell was discharged at 0.2C.The microstructure shown by field emission scanning electron microscope (FESEM) images was obtained using a Zeiss Sigma FESEM operating at 5kV at the Centre for Material Analysis of the University of Oulu. X-ray diffraction (XRD) analysis was done for the calcined NCM811 cathode materials by using Rigaku SmartLab 9 kW with Co-Kα radiation at 40 kV and 135 mA. Diffractograms were collected in the 2θ range (5–120° at 0.01° intervals). Diffraction peaks and crystallite parameters were identified using International Centre for Diffraction Data (PDF-4+ 2020). The specific surface areas, pore sizes and pore volumes of samples were determined from nitrogen adsorption desorption isotherms at the temperature of liquid nitrogen (−196 ◦C) using a Micromeritics ASAP 2020.The tapped density of powders was measured based on the ISO EN 787/11 standard. Residual lithium was measured with an automatic titrator. Particle size distribution (PSD) during the co-precipitation was measured with a Malvern Mastersizer 3000.Based on the results, co-precipitation of impurities to the NMC particles followed the thermodynamic calculations. As expected, iron, zinc, magnesium and calcium co-precipitated in NMC811 to a large extent, but potassium and lithium remain in the mother liquor. The presence of impurities was also confirmed by several characterizations. Impurities did not affect the particle morphology or tap density of NMC811. Surprisingly, the effect of impurities was also minor to the cell performance. During the cycling, these cells provided good cyclability and remain high retention (>80%) after 1100 cycles compared to reference samples.

P240 Clinical diagnostics of fecal calprotectin: a comparative study of a semi-quantitative rapid test and a quantitative lab test

Abstract Background The non-specific and heterogeneous clinical symptoms complicate the diagnosis of Inflammatory bowel disease (IBD). Colonoscopy, the primary method in IBD diagnostics, is costly and invasive, and not optimal for routine disease monitoring. Fast, user-friendly, and cost-effective diagnostic tests facilitate the timely identification of inflammation and disease monitoring. Calprotectin is a pro-inflammatory protein released by neutrophils at the intestinal mucosa, and detectable in feces. Fecal calprotectin (fCal) is a sensitive biomarker that helps to detect IBD, as its concentration is directly proportional to the degree of intestinal inflammation. Furthermore, fCal analysis helps to confirm disease activity in suspected flares and guides decision-making in drug therapy allocation. Methods In this study the accuracy of fCal detection by the semi-quantitative Actim Calprotectin rapid test and the quantitative automated LIAISON Calprotectin assay was assessed on a panel of 119 clinical stool samples. Actim Calprotectin is a visually interpreted, semi-quantitative dipstick test that is hygienically performed in a single tube. LIAISON Calprotectin is an automated quantitative chemiluminescence immunoassay (CLIA). Analyses were performed at NordLab Oulu clinical laboratory (Oulu University Hospital, Finland). Results fCal testing took only about 15 min of hands-on time with Actim Calprotectin, and 40 minutes with LIAISON Calprotectin. The mean fCal concentration in the 119 analyzed clinical samples was 191.8 μg/g (median 41.9 μg/g; range 0-6,290 μg/g) as quantified by LIAISON Calprotectin. The Actim Calprotectin and LIAISON Calprotectin assays agreed on 94 samples (79.0%) (Figure 1). The fCal concentration range-specific inter-assay agreement was as follows: 81.2% at &amp;lt; 50 µg/g, 65.6% at 50–200 µg/g, and 94.4% at &amp;gt;200 µg/g. The sensitivity of Actim Calprotectin was 94.0% (n=47) for the 50 µg/g cut-off when compared to the quantitative LIAISON Calprotectin. The three samples with fCal concentrations above 50 µg/g in the LIAISON Calprotectin test but interpreted as having fCal concentration below 50 µg/g in the Actim Calprotectin test, had an fCal concentration very close to the 50 µg/g cut-off (&amp;lt; 70 µg/g). Conclusion Actim Calprotectin is a suitable method for fCal detection in a clinical setting, supporting fast disease activity and treatment response monitoring in patients with gastrointestinal inflammation. The rapid test can be utilized for the initial differentiation between negative and positive samples in an outpatient setting, thus helping to limit the use of more laborious quantitative methods to positive samples. Future investigations could focus on evaluating the utility of Actim Calprotectin in routine disease monitoring.

No Association Between Statin Use and the Prognosis of Endometrial Cancer in Women With Type 2 Diabetes

Preclinical studies have suggested statins have antiproliferative and anti-metastatic effects on endometrial cancer cells. Similarly, most previous epidemiological studies have reported a better prognosis of endometrial cancer in patients who used statins. In this study, we explored the role of statins in the prognosis of endometrial cancer in women with type 2 diabetes in a hospital-based cohort. This retrospective cohort consisted of 119 women with type 2 diabetes who were diagnosed and treated for endometrial cancer at Oulu University Hospital, Finland, between 2007 and 2014. The patients were classified as statin users (n = 58) and nonusers (n = 61) based on the type of medication they were using at the time of endometrial cancer diagnosis. Statin use showed no association with progression-free survival or overall survival in the whole cohort nor the subgroups with type I or type II histology, in lower or higher body mass index groups, or at an early or advanced stage. The results remained similar in the multivariate analysis after adjusting for the patient’s age, cancer stage, and histology. Furthermore, statin use seemed not to have any association with most of the prognostic factors at the time of endometrial cancer diagnosis.

Preoperative measurements on MRI in Chiari 1 patients fail to predict outcome after decompressive surgery

BackgroundThe purpose of our study was to research the parameters of magnetic resonance imaging (MRI) that would predict the outcome of surgery in patients with Chiari 1 malformation (CM1) and to evaluate changes in MRI parameters after surgery.MethodsFifty-one patients (19 children, 13 adolescents, and 19 adults) operated on due to CM1 in Oulu University Hospital between 2004 and 2018 were evaluated. Seventeen parameters were measured from the preoperative MRI and 11 from the postoperative MRI. The correlations between the MRI parameters and the clinical variables before and after surgery were analyzed.ResultsThe majority (88.2%) of the patients had favorable surgical outcomes. Postoperatively, subjective symptoms improved in 88.6% of the patients and syringomyelia in 81.8%. The location of the cerebellar tonsils, when measured in relation to the C2 synchondrosis or the end plate, postoperatively moved cranially in 51.0% (n = 26), did not change in 27.4% (n = 14), and moved caudally in 21.6% (n = 11) of the patients. However, neither the location of the tonsils nor any other parameters measured from pre- or postoperative MRI correlated with the patients’ symptoms or surgical outcomes.ConclusionsNo specific parameters on preoperative MRI evaluation were predictive of the outcome of surgery, emphasizing clinical examination in surgical decision-making. Furthermore, the postoperative MRI parameters did not correlate with the surgical outcomes. Thus, routine postoperative imaging is suggested only for patients with preoperatively diagnosed syringomyelia or worsening of symptoms.

Dental fear among adolescents with cleft.

Dental fear is a prevalent phenomenon among children and adolescents globally. To investigate dental fear among 18-year-olds with cleft lip and/or palate (CLP) at their final follow-up cleft clinic visit, and to evaluate the association between dental fear and OHRQoL. This cross-sectional study included the cohort of children with CLP treated at the Oulu University Hospital Cleft Lip and Palate Center, in northern Finland since 1995. A total of 62 of 64 individuals participated in this study. The validated Finnish version of the Oral Health Impact Profile (OHIP-14) was used to assess OHRQoL. Dental fear was studied using the validated Modified Dental Anxiety Scale (MDAS) and cognitive vulnerability model (CVM). Almost two fifths of the participants reported moderate dental fear. Participants with cleft including lip and participants reporting impact on OHRQoL reported higher mean MDAS scores. In an unadjusted model, adolescents with cleft including lip had risk for higher dental MDAS scores compared with the ones with cleft including only palate. Dental fear is common among adolescents with CLP, specifically among those with clefts involving the lip. OHRQoL and dental fear seem to be associated.

Perioperative acute kidney injury and urine output in lower limb arthroplasties

This study aimed to evaluate the occurrence and perioperative risk factors of acute kidney injury (AKI) in primary elective hip and knee and emergency hip arthroplasty patients. We also aimed to assess the effect of urine output (UOP) as a diagnostic criterion in addition to serum creatinine (sCr) levels. We hypothesized that emergency arthroplasties are prone to AKI and that UOP is an underrated marker of AKI. This retrospective, register-based study assessed 731 patients who underwent primary elective knee or hip arthroplasty and 170 patients who underwent emergency hip arthroplasty at Oulu University Hospital, Finland, between January 2016 and February 2017. Of the elective patients, 18 (2.5%) developed AKI. The 1-year mortality rate was 1.5% in elective patients without AKI and 11.1% in those with AKI (P=.038). Of the emergency patients, 24 (14.1%) developed AKI. The mortality rate was 16.4% and 37.5% in emergency patients without and with AKI, respectively (P=.024). In an AKI subgroup analysis of the combined elective and emergency patients, the mortality rate was 31.3% (n=5) in the sCr group (n=16), 23.5% (n=4) in the UOP group (n=17), and 22.2% (n=2) in AKI patients who met both the sCr and UOP criteria (n=9). Emergency hip arthroplasty is associated with an increased risk of AKI. Since AKI increases mortality in both elective and emergency arthroplasty, perioperative oliguria should also be considered as a diagnostic criterion for AKI. Focusing solely on sCr may overlook many cases of AKI.

Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland.

To examine the epidemiological, clinical, and genetic characteristics of paediatric patients with genetic white matter disorders (GWMDs) in Northern Finland. A longitudinal population-based cohort study was conducted in the tertiary catchment area of Oulu University Hospital from 1990 to 2019. Patients were identified retrospectively by International Statistical Classification of Diseases and Related Health Problems codes in hospital records and prospectively by attending physicians. Inclusion criteria were children younger than 18 years with defined GWMDs or genetic disorders associated with white matter abnormalities (WMAs) on brain magnetic resonance imaging. Eighty patients (mean age [SD] at the end of the study 11y [8y 6mo], range 0-35y; 45 males, 35 females) were diagnosed with a defined GWMD. The cumulative childhood incidence was 30 per 100000 live births. Regarding those patients with 49 distinct GWMDs, 20% had classic leukodystrophies and 80% had genetic leukoencephalopathies. The most common leukodystrophies were cerebral adrenoleukodystrophy, Krabbe disease, and Salla disease. Additionally, 29 patients (36%) had genetic aetiologies not previously associated with brain WMAs or they had recently characterised GWMDs, including SAMD9L- and NHLRC2-related neurological disorders. Aetiology was mitochondrial in 21% of patients. The most common clinical findings were motor developmental delay, intellectual disability, hypotonia, and spasticity. The cumulative childhood incidence of childhood-onset GWMDs was higher than previously described. Comprehensive epidemiological and natural history data are needed before future clinical trials are undertaken. What this paper adds Forty-nine distinct genetic white matter disorders (GWMDs) were identified, with 20% of cases being classic leukodystrophies. The cumulative childhood incidence of GWMDs was higher than described previously. A considerable proportion (36%) of GWMDs were previously undefined or recently characterised GWMDs. Mitochondrial aetiology was more common (21%) than previously reported.

Emergency department admission and mortality of the non-transported emergency medical service patients: a cohort study from Northern Finland

ObjectivesA high number of emergency medical service (EMS) patients are not transported to hospital by ambulance. Various non-transport protocols and guidelines have been implemented by different EMS providers. The present...

Determining the development stage of the ossification centers around the elbow may aid in deciding whether to use ESIN or not in adolescents’ forearm shaft fractures

Background and purpose — Elastic stable intramedullary nailing (ESIN) is the preferred method of operative stabilization of unstable pediatric forearm shaft fractures. However, the decision whether to use ESIN or open reduction and internal fixation (ORIF) in older children or teenagers is not always straightforward. We hypothesized that the development stage of the elbow would aid in evaluating the eligibility of the patient for ESIN. Patients and methods — All eligible children, aged <16 years who were treated with ESIN in Oulu University Hospital, during 2010–2019 were included (N = 70). The development stages of 4 ossification centers were assessed according to the Sauvegrain and Diméglio scoring. The proportion of impaired union vs. union was analyzed according to bone maturity, by using the optimal cutoff-points determined with receiver operating characteristics (ROC). Results — Development stage ≥ 6 in the olecranon was associated with impaired union in 20% of patients, compared with none in stages 1–5 (95% CI of difference 8% to 24%). Trochlear ossification center ≥ 4 was associated with impaired union in 17% of patients (CI of difference 7% to 36%) and lateral condyle ≥ 6 in 13% of patients (CI of difference 3.4% to 30%). Proximal radial head ≥ 5.5 was associated with impaired union in 18% of patients (CI of difference 7% to 39%). Interpretation — Recognizing the rectangular or fused olecranon ossification center, referring to stage ≥ 6, was in particular associated with impaired fracture healing. This finding may aid clinicians to consider between ESIN and plating, when treating forearm shaft fracture of an older child or teenager.

Nutrition delivery after emergency laparotomy in surgical ward: a retrospective cohort study

PurposeAdequate nutrition after major abdominal surgery is associated with less postoperative complications and shorter hospital length of stay (LOS) after elective procedures, but there is a lack of studies focusing on the adequacy of nutrition after emergency laparotomies (EL). The aim of the present study was to investigate nutrition adequacy after EL in surgical ward.MethodsThe data from 405 adult patients who had undergone emergency laparotomy in Oulu University Hospital (OUH) between years 2015 and 2017 were analyzed retrospectively. Nutrition delivery and complications during first 10 days after the operation were evaluated.ResultsThere was a total of 218 (53.8%) patients who were able to reach cumulative 80% nutrition adequacy during the first 10 postoperative days. Patients with adequate nutrition (> 80% of calculated calories) met the nutritional goals by the second postoperative day, whereas patients with low nutrition delivery (< 80% of calculated calories) increased their caloric intake during the first 5 postoperative days without reaching the 80% level. In multivariate analysis, postoperative ileus [4.31 (2.15–8.62), P < 0.001], loss of appetite [3.59 (2.18–5.93), P < 0.001] and higher individual energy demand [1.004 (1.003–1.006), P = 0.001] were associated with not reaching the 80% nutrition adequacy.ConclusionsInadequate nutrition delivery is common during the immediate postoperative period after EL. Oral nutrition is the most efficient way to commence nutrition in this patient group in surgical ward. Nutritional support should be closely monitored for those patients unable to eat.Trial registration numberNot applicable.

First Type III Solar Radio Bursts of Solar Cycle 25

The minimum of the previous solar cycle, Solar Cycle 24, occurred in December 2019, which also marked the start of the new Solar Cycle 25. The first radio bursts of the new solar cycle were observed in the spring season 2020. In this work we will present three type III solar bursts which were observed in May and June 2020 at radio frequencies between 18 – 90 MHz. There are two radio observatories in Finland that are capable of doing low-frequency solar radio observations: Aalto University Metsähovi Radio Observatory (MRO) and Kilpisjärvi Atmospheric Imaging Receiver Array (KAIRA) of the Sodankylä Geophysical Observatory, University of Oulu. The instruments of the two institutes have different design and characteristics, and they operate in rather different radio interference environments. We will compare simultaneous observations from these two instruments and we will also discuss the properties of these type III solar bursts.

Interim and end-of-treatment PET-CT suffers from high false-positive rates in DLBCL: Biopsy is needed prior to treatment decisions.

The application of positron emission tomography (PET)‐computed tomography (CT) in treatment response evaluation has increased in diffuse large B‐cell lymphoma (DLBCL), although its predictive value is controversial. We retrospectively analyzed the rate of false‐positive PET‐CTs performed as interim (n = 94) and end‐of‐treatment (n = 8) assessments among 102 DLBCL patients treated during 2010–2017 at Oulu University Hospital. In PET‐CT Deauville score ≥4 was regarded as positive. A biopsy was performed on 35 patients, and vital lymphoma tissue was detected from nine patients. Positive biopsy findings were associated with poor disease outcomes in this study. This difference was statistically significant: 2‐year failure‐free survival (FFS) was 44% in patients with a positive biopsy versus 83% for those with a negative biopsy (p = 0.003). The corresponding overall survival (OS) rates were 53% versus 95% (p = 0.010). In the multivariate analyses, a negative biopsy was an independent protective factor in FFS (Hazard Ratio (HR) 0.093 (95% confidence interval [CI] 0.017–0.511); p = 0.006) unrelated to the International Prognostic Index (IPI) (HR 1.139 [95% CI 0.237–5.474] p = 0.871) or stage (HR 1.365 [95% CI 0.138–13.470]; p = 0.790). There was no statistically significant difference in OS according to the PET results, but the FFS rate was significantly higher in patients with a negative PET. The value of PET‐CT as an evaluation method suffers from a high false‐positive rate, and it is inadequate alone for the justification of treatment decisions. Biopsy results provide more reliable prognostic information for the evaluation of treatment response and outcome and should be used to assess patients with positive PET‐CT scans.

Is cytochrome c oxidase subunit I (COI) the right DNA barcoding marker for the Chaetopteryx villosa group?

Chaetopteryx villosa (Fabricius, 1798) is a caddisfly species distributed throughout Europe, except in the Balkan and Apennine Peninsula. However, phylogenetically close species belonging to the C. villosa group are widespread throughout entire Europe. Species of this group (C. villosa, C. gessneri, C. fusca, C. sahlbergi, C. atlantica, C. bosniaca, C. vulture, and C. trinacriae) have distinct distributions with some overlaps. Adult forms of these species are morphologically similar, whereas larval morphology is only known for some species. There are also indications of species hybridization (e.g., C. villosa x fusca). Presumably, the molecular approach for the species determination of this group would be highly beneficial. In the BOLD database, there are 154 specimens with COI-5P barcodes of C. villosa species. Out of the remaining species, C. sahlbergi has 27 specimens with a barcode, C. fusca 20, C. gessneri 5, C. bosniaca 5, and C. atlantica 1, whereas sequences from the species C. vulture and C. trinacriae are missing. Therefore, we tested the power of discrimination of the COI-5P marker in the C. villosa group, as the most common barcoding markers for species identification in animals. Only sequences from public records originating from experienced research groups or taxonomists and containing a specimen photograph were taken as input. A total of 75 sequences from the BOLD database were obtained. Out of these sequences, 11 belonged to C. fusca, 5 to C. gessneri, 52 to C. villosa, 5 to C. bosniaca, and 2 to C. sahlbergi. For the generation of overview trees, COI-5P barcodes of Rhyacophila fasciata and Rh. nubila were used as outgroups. All sequences were trimmed at 5’ and 3’ ends, resulting in a final alignment length of 516 base pairs. Multiple sequence alignments and editing were done in the MEGA-X software. Analysis of nucleotide polymorphism was done in DNASP6 software. MEGA-X was used to calculate the pairwise distance and overall mean p-distance, and to construct the overview trees. Analysis of DNA polymorphism revealed 14 haplotypes of C. villosa, 3 haplotypes of C. fusca, 2 haplotypes of C. gessneri, and one for species C. bosniaca and C. sahlbergi. There were no significant interspecific and intraspecific differences among haplotypes based on pairwise distances. The p-distance between one of the haplotypes of C. fusca and C. villosa was 0.000, whereas the p-distance among haplotypes of C. villosa varied from 0.001 to about 0.055. The mean overall p-distance among haplotypes of all species equaled 0.03. No species-specific clusters were observed when phylogenetic trees were constructed except for C. gessneri, regardless of the method used (i.e., NJ, UPGMA, ML, ME, or MP). To minimize the possibility of species misidentification, we used only records submitted by NTNU-Norwegian University of Science and Technology (Norway), SNSB-Zoologische Staatssammlung Muenchen (Germany), Zoologisches Forschungsmuseum Alexander Koenig (Germany), University of Oulu, Zoological Museum (Finland), prof Hans Malicky and prof Mladen Kučinić. No records identified as hybrids were included in the analyses. With the exception of C. gessneri, COI-5P marker failed to separate the species of the C. villosa group. However, it is highly unlikely that poor species determination was the basis for such a result. To enable the comprehensive and unbiased evaluation of the relationships within this group, data coverage in BOLD database for most of the studied species should be enhanced, encompassing different geographical distribution of samples. Further studies are needed to detect the array of molecular markers suitable for the species delineation in a complex group such as C. villosa.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: Relapse and Tonsillar Regrowth After Childhood Tonsillectomy

Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, but the role of adenoidectomy, as well as later tonsillar regrowth, is unclear. To find out if the volume of lymphoid tissue is pivotal to the efficacy, we analyzed the association between the relapse of the symptoms of PFAPA syndrome and regrowth of tonsillar tissue after tonsillectomy or adenotonsillectomy. Prospective cohort study of operated PFAPA pateints. We invited all patients that had undergone tonsillectomy or adenotonsillectomy due to PFAPA syndrome at the Oulu University Hospital, Oulu, Finland, between the years 1990 and 2007, at the age of ≤12 years, to a follow-up visit, after an average period of 9.8 years after their diagnoses. Out of the 132 invited, 94 (71%) participated in the follow-up study. At the follow-up study visit, 5 (5%) of the 94 PFAPA syndrome cases experienced recurrent fevers. The regrowth of palatine tonsillar tissue was seen in four of them (80%) as compared to 19/89 (21%) of symptom-free patients (P = .006). Two of the patients with clear PFAPA relapse at the time of the study visit were reoperated with clear effect on the symptoms. At the time of the study visit, 59/63 (94%) of the patients who had undergone adenotonsillectomy and 30/31 of the patients (97%) who had undergone tonsillectomy earlier were free of fever flares (P = .99). Palatine tonsil regrowth was associated with PFAPA syndrome relapse after tonsillectomy. Reoperation might be a treatment option in these patients. 4 Laryngoscope, 2021.

Measures of empathy and the capacity for self-reflection in dental and medical students

BackgroundEmpathy and self-reflection have been studied among medical students, but fewer studies have examined the presence of these attributes among dental students and investigated the correlation between empathy and self-reflection.MethodsFirst-year dental and medical students (n = 198) beginning their studies at the University of Oulu, Finland in August 2017 participated in this study, which was conducted via an internet-based questionnaire. Data were collected on personal characteristics and scores on Davis’s Interpersonal Reactivity Index (IRI) and Roberts’s Self Reflection and Insight Scale (SRIS).ResultsDifferences in IRI scores between dental and medical students were significant only in male students and in two IRI domains. Mean (SD) scores for male dental and medical students were personal distress, 8.2 (4.0) and 10.7 (3.1) (p = 0.022); empathic concern, 15.0 (4.0) and 16.9 (3.5) (p = 0.054). Mean SRIS scores did not differ between sexes or training programs. Positive correlations (r = − 0.3–0.65) were observed between some empathy and self-reflection subscales.ConclusionsA lower degree of empathy was observed among male dental students than in male medical students. A positive correlation between empathy and self-reflection was demonstrated in both study groups and sexes. However, more research in this field is warranted.

Profile of Substance Misuse among Adolescent and Young Adult Gabapentinoid Users: A Register-Based Follow-up Study of Former Adolescent Psychiatric Inpatients

Aims: Our study examined characteristics of adolescent and young adult study participants using gabapentinoids (gabapentin, pregabalin), with previous history of adolescent psychiatric inpatient hospitalization. Particular focus was on temporal association of age, at first prescription for gabapentinoids, to age at tobacco smoking initiation, regular alcohol use, diagnosis of substance dependence and prescriptions for benzodiazepines and opioids. Methods: The initial study population contained 508 adolescents (300 females, 208 males) admitted to psychiatric inpatient care in Oulu University hospital between the ages 13–17 years. Register-based follow-up information on prescriptions for gabapentinoids, benzodiazepines and opioids, as well as ICD-10 diagnosis for hospital-treated substance dependence, was obtained from the Finnish national health care registers. Results: The users of gabapentinoids accounted for 9.1% of the initial study population. Of adolescence-related characteristics, suicidal ideation, suicide attempts and non-suicidal self-injury was emphasized in females using gabapentinoids. The majority of participants using gabapentinoids had benzodiazepines (80.4%) and opioids (71.7%) as comorbid drugs. Initiation of tobacco smoking and alcohol use and first prescriptions for of benzodiazepines and opioids, and a diagnosis of substance dependence commonly predated first prescriptions for gabapentinoids. Conclusions: In clinical practice, the decision to prescribe gabapentinoids to adolescents or young adults must be made with caution, particularly for those with substance use problems and/or without a clinically approved indication.

Metformin Associates With Aggressive Features of Endometrial Cancer in Women With Type 2 Diabetes.

Preclinical studies on metformin use and endometrial cancer have been promising but epidemiological studies have reported variable results. This study aimed to assess if metformin use is associated with endometrial cancer aggressiveness and survival in women with type 2 diabetes (T2D). This retrospective hospital-based cohort consisted of women with T2D who were treated for endometrial cancer at the Oulu University Hospital, Finland, between 2007 and 2014. The sample size was 121 patients: 58 metformin users and 63 metformin non-users. Intriguingly, type 2 histology, deep myometrial invasion and the presence of lymphovascular invasion were more common in the metformin user group. However, metformin use showed no association with overall survival and progression-free survival. Metformin use was associated with poorer prognostic factors in endometrial cancer patients with T2D.